The present invention relates to a method and apparatus for the generation of a high purity chromatography eluent, particularly a gradient eluent.
In practicing liquid chromatography, a sample containing multiple components is directed through a chromatography medium contained typically in an ion exchange resin bed. The components are separated on elution from the bed in a solution of eluent.
One effective form of liquid chromatography is referred to as ion chromatography. In this known technique, the ions in the sample solution are directed through a chromatographic separation stage using such eluent containing an electrolyte and thereafter to a suppression stage, followed by detection, typically by an electrical conductivity detector. In the suppression stage, the electrical conductivity of the electrolyte is suppressed but not that of the separated ions so that the latter may be detected by a conductivity cell. This technique is described in detail in U.S. Pat. Nos. 3,897,213, 3,920,397, 3,925,019 and 3,956,559.
Suppression or stripping of the electrolyte by an ion exchange resin bed is described in the prior art references. A different form of suppressor is described in EPA Pub. No. 32,770 published July 29, 1981. Here, an ion exchange membrane in the form of a fiber or sheet is used in place of the resin bed. In the sheet form, the sample and eluent are passed on one side of the sheet and a flowing regenerant is passed on the other side of the sheet. The sheet is in the form of an ion exchange membrane partitioning regenerant from the effluent of chromatographic separation. The membrane passes ions of the same charge as the exchangeable ions of the membrane to convert the electrolyte of the eluent to weakly ionized form, followed by detection of the ions.
An improved membrane suppressor device is disclosed in EPA Pub. No. 75,371, published Mar. 30, 1983. There, a hollow fiber suppressor is packed with polymer beads to reduce band spreading. There is a suggestion that such packing may be used with other membrane forms. Furthermore, there is a suggestion that the function of the fiber suppressor is improved by using ion exchanger packing beads. No theory is set forth as to why such particles would function in an improved manner.
Another suppression system is disclosed in EPA Pub. No. 69,285, published Jan. 12, 1983. There, the effluent from a chromatographic column is passed through a central flow channel defined by flat membranes on both sides of the channel. On the opposite sides of both membranes are regenerant channels through which the regenerant solutions are passed. As with the fiber suppressor, the flat membranes pass ions of the same charge as the exchangeable ions of the membrane. An electric field is passed between electrodes on opposite sides of the effluent channel which is stated to increase the rate of suppression. One problem with this electrodialytic membrane suppressor (EDS) system is that very high voltages (50-500 volts DC) are required. As the liquid stream becomes deionized, electrical resistance increases, resulting in substantial heat production. Such heat is detrimental to effective detection because it greatly increases noise and decreases sensitivity. Another problem is that the system generates excessive quantities of hydrogen gas.
An improved form of suppressor is described in EPA Pub. No. 180,321, published May 7, 1986. In this apparatus, the suppressor includes at least one regenerant compartment and one effluent compartment separated by an ion exchange membrane sheet. The sheet allows transmembrane passage of ions of the same charge as its exchangeable ions. Ion exchange screens are used in the regenerant and effluent compartments. Flow from the effluent compartment is directed to a detector, such as an electrical conductivity detector, for detecting the resolved ionic species. The screens provide ion exchange sites and serve to provide site to site transfer paths across the effluent flow channel. A sandwich suppressor is also disclosed including, a second membrane sheet opposite to the first membrane sheet and defining a second regenerant compartment. Spaced electrodes are disclosed in communication with both regenerant chambers along the length of the suppressor. By applying an electrical potential across the electrodes, there is an increase in the suppression capacity of the device.
Another EDS is disclosed in U.S. Pat. No. 4,403,039. An anode is disposed in the center of a tubular ion exchange membrane surrounded by a concentric annular flow channel and a tubular cathode.
An electrolytic membrane suppressor (EMS) is disclosed in Strong, D.L.; Dasgupta, P.K.; Anal. Chem. 1989, 61 939-945. That paper discloses single and double membranes in concentric tubular form. In the eluent which is suppressed, sodium ion passes to an annular regenerant solution container fed with water so that the effluent from such regenerant chamber is sodium hydroxide.
There is a general need for high purity eluents for liquid chromatography and a particular need in ion chromatography. Similarly, there is a need for a convenient way to generate gradient eluents of precise concentrations and timing. Gradient eluents are eluents at different strengths and concentrations used during the course of a single chromatography run. The use of gradient eluents for ion chromatography is described in Rocklin, R.D., et al. J. of Chromatographic Science, Vol. 27, p. 474, Aug. 1989; Qi, D., et al. Analytical Chemistry, Vol. 61, p. 1383, 1989; and Shintani, H., et al., Analytical Chemistry, Vol. 59, p. 802, 1987.